Treatment Of Pneumonia Research Articles

DDDR-11. INHIBITING OXIDATIVE PHOSPHORYLATION AND HYPOXIA WITH ATOVAQUONE – A STRATEGY TO RADIOSENSITIZE DIFFUSE MIDLINE GLIOMA

Abstract Diffuse midline glioma (DMG) is a uniformly fatal paediatric brainstem tumour with median survival of less than 1 year. Radiotherapy has been the only effective treatment for decades, but most DMGs recur within several months due to radioresistance. The hypoxic tumour microenvironment is a main feature of solid tumours including gliomas and a major contributor to radioresistance. Therefore, alleviating tumour hypoxia to enhance the effectiveness of radiotherapy is a potential therapeutic strategy to improve the survival outcomes of DMG patients. We found evidence suggesting increased mitochondrial oxidative phosphorylation (OXPHOS) in DMG. Hence, we aimed to target OXPHOS by decreasing the oxygen consumption rate (OCR) of DMG cells, which in turn will alleviate hypoxia by sparing more oxygen and subsequently improve the radiosensitivity of DMG cells. We performed a high-throughput screening to identify potent OCR inhibitors from a library of 1963 FDA-approved drugs. The most promising OCR inhibitor identified was atovaquone, a drug used for treatment of pneumocystis pneumonia and malaria. We found that atovaquone inhibited mitochondrial metabolism of DMG cells by specifically targeting the mitochondrial complex III. Increased mitochondrial reactive oxygen species after exposure to atovaquone suggested that it increases oxidative stress. The treatment alleviated hypoxia and decreased the expression of hypoxia-inducible factor-1a in 3-dimensional DMG neurospheres and improved the radiosensitivity in several DMG cultures. To overcome the poor bioavailability of commercially available atovaquone that results in low therapeutically effective brain concentrations, we tested its efficacy against the amorphous solid dispersion (ASD) atovaquone formulation which appears to enhance atovaquone levels in the brain. We found that both the formulations inhibited OCR and hypoxia at similar doses and enhanced DMG radiosensitivity. The combination of ASD atovaquone and radiation significantly improved survival in orthotopic DMG mouse model. Collectively, this data provides evidence of atovaquone as a potential radiosensitizer for DMG.

A comparative study between methylprednisolone versus dexamethasone as an initial anti-inflammatory treatment of moderate COVID-19 pneumonia: an open-label randomized controlled trial

Abstract Background The most appropriate anti-inflammatory treatment for moderate COVID-19 pneumonia remains uncertain. We aimed to compare the effectiveness of a high-dose methylprednisolone versus a high-dose dexamethasone in hospitalized moderate COVID-19 pneumonia, regarding the WHO clinical progression scales, mortality, and the length of hospitalization. Methods In this open-labeled randomized controlled trial, we enrolled patients with age > 18 years old who were diagnosed moderate COVID-19 pneumonia confirmed by real-time PCR, evidence of pneumonia by chest imaging and resting oxygen saturation between 90 and 94%. Patients were randomized at a 1:1 ratio to receive methylprednisolone 250 mg/day or dexamethasone 20 mg/day over the first three days. Then the patients in both groups received dexamethasone 20 mg/day on days 4–5, and 10 mg/day on days 6–10. Primary outcome was assessed by a 10-point WHO clinical progression scales ranging from uninfected (point 0) to death (point 10) on the fifth day of treatment. Secondary outcomes including 90-day mortality, length of hospitalization, rate of intensive care unit (ICU) transfer and complications were determined. Results Of 98 eligible patients, the mean age was 76.0 ± 13.3 years. The median date of illness at the time of randomization was 3 days (interquartile range 2, 5). Baseline clinical characteristics and severity did not differ between groups. The WHO clinical progression scales were similar between methylprednisolone and dexamethasone group at 5 and 10 days of treatment [4.84, (95% confidence interval(CI), 4.35–5.33) vs. 4.76 (95% CI, 4.27–5.25), p = 0.821 and 4.32 (95% CI, 3.83–4.81) vs. 3.80 (95% CI, 3.31–4.29), p = 0.140, respectively)]. Both groups did not differ in-hospital mortality, length of hospitalization, and rate of ICU transfer. There were also no differences in steroid-related complications between groups until 90 days of follow-up. Conclusions In patients with moderate COVID-19 pneumonia, initial anti-inflammatory treatment with 250 mg/day of methylprednisolone for three days does not yield better outcomes over high-dose dexamethasone. Trial registration This study was registered at Thai Clinical Trials Registry on October 17, 2021, with the identifier TCTR20211017001.

A Mucous Permeable Local Delivery Strategy Based on Manganese-Enhanced Bacterial Cuproptosis-like Death for Bacterial Pneumonia Treatment.

Bacterial pneumonia is one of the most challenging global infectious diseases with high morbidity and mortality. Considering the antibiotic abuse and resistance of bacterial biofilms, a variety of metal-based materials have been developed. However, due to the high oxygen environment of the lungs, some aerobic infection bacteria have high tolerance to oxygen and ROS, and most of the metal-based materials based on ROS may not achieve good therapeutic effects. Inspired by the sensitivity of cuproptosis to aerobic respiratory cells, we designed a copper composite antibacterial nanoparticle and found that it can effectively induce cuproptosis-like death in the aerobic bacteria of the lungs. To address the challenge of in vivo application of cuproptosis, manganese dioxide was first incorporated to deplete protective glutathione, which can interact with copper and thus hinder the interaction of copper with proteins and assist in antibacterial action through immune enhancement. Cuproptosis-like death also requires a large number of copper ions. To meet this demand, we deliver positively hydrophilic modified composite nanoparticles that effectively penetrate the lung mucus layer directly to the lungs through local administration, and the copper ions are further released rapidly by the acidic environment at the infected site, which can further destroy bacterial biofilms in synergy with manganese. This drug-delivery system can effectively treat pneumonia caused by aerobic bacteria and avoid systemic toxicity that can be caused by large doses of copper.

The effect and safety of corticosteroid treatment for severe community-acquired pneumonia: a meta-analysis of randomized controlled trials

BackgroundThere is ongoing debate on the efficacy and safety of corticosteroid therapy for severe community-acquired pneumonia (sCAP). Our aim was to investigate the safety and therapeutic effectiveness of corticosteroids in the sCAP therapy.MethodsElectronic databases (Cochrane Library, PubMed, Web of Science and Embase) were searched from inception to January 10, 2024. We examined for randomized controlled studies assessing the effectiveness and safety of corticosteroid therapy in individuals with sCAP. The primary outcome was short-term mortality. Subgroup analyses were carried out according to the corticosteroid type. Additionally, trial sequential analysis (TSA) was carried out.ResultsIn total, 11 trials, including 1959 patients, met the predetermined standards and underwent analysis. Overall, our meta-analysis exhibited that corticosteroids may considerably lower short-term mortality when compared to control treatment [6 studies (1,582 patients); odds ratio (OR), 0.65; 95% confidence interval (CI) 0.49–0.88; p = 0.005] and C-reactive protein (CRP) levels [5 studies (359 patients); mean difference (MD), −6.97; 95% CI −12.33 to −1.60; p = 0.01], but TSA revealed that the sample size needs to be larger. Moreover, we observed that corticosteroids reduced the hospital length of stay [7 studies (999 patients); MD, −3.56; 95% CI, −4.28 to −2.84; p < 0.001], need for mechanical ventilation (MV) [7 studies (1,328 patients); OR, 0.60; 95% CI, 0.45–0.79; p = 0.001] and MV duration [4 studies (736 patients); MD, −5.62; 95% CI, −7.31 to −3.94; p < 0.001], which was in agreement with TSA. However, adverse events, length of hospital and intensive care unit (ICU) stay were not evidently shortened when TSA was utilized. Furthermore, subgroup analysis revealed that all of the above studies benefited from hydrocortisone treatment in comparison to the control group.ConclusionOur meta-analysis revealed that corticosteroids, especially hydrocortisone, could decrease the mortality of individuals with sCAP.Systematic review registration[https://clinicaltrials.gov/], identifier [CRD42023415555].

Streptococcus salivarius pneumonia-associated pneumomediastinum: a case report and literature review

BackgroundStreptococcus salivarius is an opportunistic pathogen, and there have been no reported cases of Streptococcus salivarius pneumonia to date. Pneumomediastinum is usually secondary to tracheal or esophageal injury and is very rare as a complication of pneumonia. We report a case of Streptococcus salivarius pneumonia complicated by pneumomediastinum, aiming to enhance clinicians’ awareness of rare pathogens and uncommon complications in pneumonia.Case presentationThe patient, a 36-year-old male, presented with a persistent cough and sputum production for one week, accompanied by a sore throat that had developed just one day prior. Chest computed tomography (CT) disclosed pneumomediastinum alongside obstructive atelectasis in the left lower lobe. Streptococcus salivarius infection was conclusively identified through bronchoalveolar lavage metagenomic next-generation sequencing (mNGS), as well as smear and culture analyses. The patient was administered intravenous amoxicillin-clavulanate potassium for a duration of seven days as part of the anti-infection regimen. Given the stability of the patient’s respiratory and circulatory systems, a tube drainage procedure was deemed unnecessary. Post-treatment, the patient’s clinical symptoms notably improved. A subsequent chest CT scan revealed the re-expansion of the left lower lung and near-complete resolution of pneumomediastinum.ConclusionThere are numerous pathogens that can cause pneumonia. While focusing on common pathogens, it is important not to overlook rare ones. When considering infections from rare pathogens, it is recommended to promptly perform a bronchoscopy and submit bronchoalveolar lavage fluid for mNGS to improve pathogen detection rates. During the diagnosis and treatment of pneumonia, it is crucial to be vigilant for rare complications. When a patient presents with symptoms such as dyspnea or subcutaneous emphysema, it is advisable to immediately perform a chest CT scan to rule out pneumomediastinum.

Investigating the role of PmrB mutation on Colistin antibiotics drug resistance in Klebsiella Pneumoniae

Klebsiella pneumoniae, a member of the Enterobacteriaceae family, naturally resides in the digestive tracts of both healthy animals and humans. Carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant health risk for hospitalized patients worldwide, greatly reducing the effectiveness of commonly used antibiotics. This leaves healthcare providers with limited treatment options, often relying on colistin. PmrB is important for the survival of Klebsiella pneumonia and, a mutation in the PmrB protein is accountable for the development of colistin antibiotic resistance in Klebsiella pneumonia. This is especially important because colistin is a fundamental component in the treatment of pneumonia. Three mutated residues—T157P, G207D, and T246A—are responsible for colistin resistance. The structural alterations and underlying mechanisms in the PmrB protein that cause resistance owing to mutation remain unclear. As a result, this study is focused to the exploration of the putative mechanism of resistance resulting from these mutations, as well as the structure modification of normal and mutant PmrB proteins, using molecular docking and molecular dynamics simulations analysis. Our results demonstrated that the interaction paradigm for the mutants has been altered and thus showing a significant effect upon the hydrogen bonding network. Interestingly, the binding of Colistin with the three mutant demonstrate unstable behavior as compared with WT+Colistin. The proposed drug-resistance mechanism will help to guide the development of PmrB drugs. These finding may give a new framework for developing novel drugs against the mutant version of PmrB.

Cost-effectiveness of a short-course antibiotic treatment strategy for the treatment of ventilator-associated pneumonia: an economic analysis of the REGARD-VAP trial

Cost-effectiveness of a short-course antibiotic treatment strategy for the treatment of ventilator-associated pneumonia: an economic analysis of the REGARD-VAP trial

Working group summary of the 2023 full update of the Finnish national guidelines for paediatric lower respiratory tract infections.

The first evidence-based Finnish guidelines for paediatric lower respiratory tract infections (LRTIs) were published in 2014 and completely updated in 2023. This paper, by the interdisciplinary working group that developed the 2023 guidelines, summarises the main recommendations. The 2023 guidelines were produced after a systematic review. Strong evidence was at least two separate, high-quality studies, moderate evidence was at least one high-quality study and weak evidence was at least one satisfactory study. The authors have now summarised the key points. There was strong evidence that antitussives and beta-sympathomimetics were not effective for bronchitis-related cough and that laryngitis should be treated with oral corticosteroids, with adrenaline inhalations added in severe cases. Also, that amoxicillin for 5 days provided sufficient treatment for paediatric community-acquired pneumonia and that children with apparent viral pneumonia could be observed without antimicrobial therapy. There was moderate evidence that corticosteroids or inhaled agents were not effective for bronchiolitis and that administering salbutamol with a holding chamber could relieve symptoms of wheezing bronchitis. Also, pertussis should be considered for unvaccinated infants with coughs. The 2023 guidelines aim to improve acute evidence-based treatment of LRTIs, through appropriate antibiotics, inhaled drugs, corticosteroids, radiology and laboratory testing.

Exploration of the Active Components and Mechanism of Jiegeng (Platycodonis Radix) in the Treatment of Influenza Virus Pneumonia Through Network Pharmacology Analysis and Experimental Verification

ABSTRACTThis study aimed to explore the pathogenesis of platycodin D and luteolin, which are both active components in Jiegeng (Platycodonis Radix), in the treatment of influenza virus pneumonia through network pharmacology analysis combined with experimental verification. The bioactive components of Jiegeng (Platycodonis Radix) were screened by TCMSP and literature mining, and the results were standardized via the UniProt database. The action targets for the disease were identified from databases including OMIM, GeneCards, TTD, DisGeNET, and PharmGKB. Then, the visualized key target regulatory network and protein–protein interaction (PPI) network for the active components were established using Cytoscape3.7.1 software. The findings were illustrated through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The intervention concentrations of platycodin D and luteolin were screened by the CCK8 method, and the important signaling pathways of platycodin D and luteolin for treating influenza virus pneumonia were verified by RT‐qPCR and Western blot tests. From data mining, 89 common drug‐disease targets were screened out, and five major active components of Jiegeng (Platycodonis Radix), including platycodin D and luteolin, were obtained. Besides, 11 therapeutic targets including IL‐17, IL‐6, TNF‐α, JUN, and MAKP1 were identified by PPI network analysis. GO and KEGG enrichment analyses showed that the pathways most related to the mechanisms of Jiegeng (Platycodonis Radix) against influenza virus pneumonia included the TNF and IL‐17 signaling pathways and apoptosis. In vitro experiments demonstrated that the model group exhibited a notable elevation in mRNA levels of IL‐6, IL‐17, TNF‐α, JUN, MAPK1, and the IL‐17/−acting protein ratio, as compared to the control group (p < 0.05). In contrast to the model group, the IL‐6, IL‐17, TNF‐α, JUN, MAPK1 mRNA expression levels, and the IL‐17 protein ratio in both the platycodin D group and luteolin group were considerably decreased (p < 0.05). Combined with network pharmacology and experimental verification, this study revealed that platycodin D and luteolin in Jiegeng (Platycodonis Radix) may treat influenza virus pneumonia by regulating inflammation through the IL‐17 signaling pathway.

Flexible Development Programs for Antibacterial Drugs to Address Unmet Medical Needs.

The US Food and Drug Administration recognizes the unmet medical need for antibacterial drugs to treat serious bacterial diseases caused by resistant pathogens for which effective therapies are limited or lacking. The agency also recognizes that designing and conducting clinical trials to assess the safety and efficacy of drugs to treat resistant infections is challenging, especially for drugs only active against a single or a few bacterial species, and that a more flexible development program might be appropriate. In this article, we discuss several regulatory considerations for flexible development programs for antibacterial drugs intended to meet an unmet medical need. As an example, we use the recent approval of sulbactam for injection and durlobactam for injection (XACDURO) for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible isolates of Acinetobacter baumannii-calcoaceticus complex.

Non-inferiority trial in veal calves on the efficacy of oxytetracycline and florfenicol treatment for pneumonia guided by quick thoracic ultrasound

Non-inferiority trial in veal calves on the efficacy of oxytetracycline and florfenicol treatment for pneumonia guided by quick thoracic ultrasound

Targeted delivery of flagellin by nebulization offers optimized respiratory immunity and defense against pneumococcal pneumonia.

Novel therapeutic strategies are urgently needed to combat pneumonia caused by Streptococcus pneumoniae strains resistant to standard-of-care antibiotics. Previous studies have shown that targeted stimulation of lung innate immune defenses through intranasal administration of the Toll-like receptor 5 agonist flagellin improves the treatment of pneumonia when combined with antibiotics. To promote translation to the clinic application, this study assessed the direct delivery of flagellin to the airways through nebulization using a vibrating mesh nebulizer in mice. Intranasal delivery achieved approximately 40% lung deposition of the administered flagellin dose, whereas nebulization yielded less than 1%. Despite these differences, nebulized flagellin induced transient activation of lung innate immunity characterized by cytokine/chemokine production and neutrophil infiltration into airways analogous to intranasal administration. Furthermore, inhalation by nebulization resulted in an accelerated resolution of systemic pro-inflammatory responses. Lastly, adjunct therapy combining nebulized flagellin and amoxicillin proved effective against antibiotic-resistant pneumococcal pneumonia in mice. We posit that flagellin aerosol therapy represents a safe and promising approach to address bacterial pneumonia within the context of antimicrobial resistance.

Case report: Mixed hydrofluoric and nitric acid mist inhalation poisoning

IntroductionHydrofluoric and nitric acids are strongly acidic substances with strong oxidation and are widely used in industrial production. Chemical pneumonia caused by the inhalation of strong acids has occasionally been reported. Severe chemical pneumonia can lead to acute pulmonary edema and life-threatening acute respiratory distress syndrome. The treatment of chemical pneumonia mainly relies on symptomatic and supportive treatment such as anti-inflammatory and anti-infection.Case descriptionThis study reports three cases of chemical pneumonia caused by the inhalation of a mixed hydrofluoric and nitric acid mist during an occupational exposure accident. After appropriate emergency symptomatic treatment, such as oxygenation and excretion promotion, cough, and difficulty in breathing were alleviated but not completely cleared.DiscussionMost of the literature reports damage caused by hydrogen fluoride on the skin and mucosal burns, and reports on lung damage caused by the inhalation of large amounts of hydrogen fluoride gas are relatively rare. Usually in the early stage of this kind of patients can have elevated blood picture, hypoxemia, pulmonary CT inflammatory plaque changes, so as to have obvious respiratory irritation symptoms. When inhaling a large amount of hydrofluorine mixed nitric acid mist, in addition to considering the occurrence of severe pneumonia, we should also be alert to the occurrence of other organ damage and electrolyte disorder.ConclusionAs occupational hydrogen fluoride gas inhalation poisoning often occurs in groups, improving the safety facilities and standard operations of small- and medium-sized enterprises is necessary. For medical workers, it is necessary to be alert to the occurrence of severe toxic pneumonia and severe fluorosis.

A Comparison of Different Strategies for Optimizing the Selection of Empiric Antibiotic Therapy for Pneumonia Caused by Gram-Negative Bacteria in Intensive Care Units (ICUs): Unit-Specific Combination Antibiograms Versus Patient-Specific Risk Factors

Abstract Background Guidelines suggest dual anti-pseudomonal therapy for empiric treatment of pneumonia caused by Gram-negative bacteria in ICU patients. Additionally, consideration of local susceptibility data and patient-specific risk factors for resistance is recommended for selecting optimal empiric regimens. However, data assessing how to best do this are lacking, and it is unclear whether a local susceptibility data-based or a patient specific risk factor-based approach will better drive appropriate empiric treatment. This study aims to compare these two strategies. Methods This retrospective study was divided into two periods. In period I, Gram-negative respiratory cultures from ICU patients were used to develop unit-specific combination antibiograms, and individual patient charts were reviewed to assess the impact of risk factors on antimicrobial susceptibility to develop a risk-factor based treatment algorithm. Optimal empiric regimens based on these two strategies were then defined. In period II, these regimens were hypothetically applied to patients to compare rates of appropriate empiric therapy and overuse by the two methods. Results Risk factor-based regimens had a higher appropriateness rate compared to regimens derived from antibiograms (89.9% vs 83.7%). Additionally, applying antibiogram based regimens resulted in a higher prevalence of antibiotic overuse than a patient-specific risk factor based approach (69.8% vs. 40.3%), with excess overuse driven by a higher frequency of unnecessary use of combination therapy. Conclusion Both strategies provided high rates of appropriateness in empiric antibiotic selection. However, the patient-specific risk factor-based approach demonstrated a higher rate of appropriate therapy and offered advantages in reducing rates of unnecessary combination therapy.

Lefamulin dosing optimization using population pharmacokinetic and pharmacokinetic/pharmacodynamic assessment in Chinese patients with community-acquired bacterial pneumonia

PurposeLefamulin is the first pleuromutilin antibiotic approved for the treatment of community-acquired bacterial pneumonia (CABP). However, the pharmacokinetic/pharmacodynamic (PK/PD) characteristics in Chinese CABP patients are not fully understood. This study aimed to evaluate its microbiological efficacy against Streptococcus pneumoniae and Staphylococcus aureus via PK/PD analysis.MethodsThe population PK (PopPK) model, established with foreign data was validated using data from Chinese CABP patients. PK/PD analysis was conducted for the intravenous administration of 150 mg q12 h for 1-h, 1.5-h and extended 2-h infusion. Oral administrations of 600 mg q12 h were assessed, considering original and higher plasma protein binding.ResultsLefamulin displayed similar PK characteristics in both Chinese and Western populations. The PopPK model effectively predicted lefamulin concentrations in Chinese CABP patients. Under the dosage regimen of 150 mg q12 h via intravenous infusion for 1/1.5/2 h, the probability of target attainments reached 98% at the minimum inhibitory concentration for both 90% S. pneumoniae and S. aureus, considering both original and higher protein binding rates. It is advisable to extend the infusion duration from 1/1.5 h–2 h to minimize the risk of adverse effects at the infusion site. Regardless of fasted or fed conditions, the PTAs for 600 mg q12 h lefamulin via oral administration proved comparable to those for intravenous administration.ConclusionThis study proved that intravenous and oral administrations of lefamulin can reach preclinical PK/PD targets of S. pneumoniae and S. aureus. These findings support the optimal use of lefamulin for the safe and effective treatment of Chinese CABP patients.

Comparative safety of different antibiotic regimens for the treatment of outpatient community-acquired pneumonia among otherwise healthy adults.

Evidence is limited about the comparative safety of antibiotic regimens for treatment of community-acquired pneumonia (CAP). We compared the risk of adverse drug events (ADEs) associated with antibiotic regimens for CAP treatment among otherwise healthy, non-elderly adults. We conducted an active comparator new-user cohort study (2007-2019) of commercially-insured adults 18-64 years diagnosed with outpatient CAP, evaluated via chest x-ray, and dispensed a same-day CAP-related oral antibiotic regimen. ADE follow-up duration ranged from 2-90 days (e.g., renal failure [14 days]). We estimated risk differences [RD] per 100 treatment episodes and risk ratios using propensity score weighted Kaplan-Meier functions. Ankle/knee sprain and influenza vaccination were considered as negative control outcomes. Of 145,137 otherwise healthy CAP patients without comorbidities, 52% received narrow-spectrum regimens (44% macrolide, 8% doxycycline) and 48% received broad-spectrum regimens (39% fluoroquinolone, 7% β-lactam, 3% β-lactam + macrolide). Compared to macrolide monotherapy, each broad-spectrum antibiotic regimen was associated with increased risk of several ADEs (e.g., β-lactam: nausea/vomiting/abdominal pain [RD per 100, 0.32; 95% CI, 0.10-0.57]; non-Clostridioides difficile diarrhea [RD per 100, 0.46; 95% CI, 0.25-0.68]; vulvovaginal candidiasis/vaginitis [RD per 100, 0.36; 95% CI, 0.09-0.69]). Narrow-spectrum antibiotic regimens largely conferred similar risk of ADEs. We generally observed similar risks of each negative control outcome, indicating minimal confounding. Broad-spectrum antibiotics were associated with increased risk of ADEs among otherwise healthy adults treated for CAP in the outpatient setting. Antimicrobial stewardship is needed to promote judicious use of broad-spectrum antibiotics and ultimately decrease antibiotic-related ADEs.

Beneficial effect of sequential treatment with high-dose steroids and short-course oral glucocorticoids in patients with severe influenza virus-associated pneumonia

Accumulating evidence supports that glucocorticoid treatment for viral pneumonia (VPA) can shorten the disease course and improve survival. However, currently, the use of glucocorticoids in treating VPA remains controversial. Moreover, a unified standard for the dosage and duration of glucocorticoid therapy has not been presented in published articles. A retrospective analysis was conducted in patients who were hospitalized for severe influenza virus-associated pneumonia, and they received sequential treatment with high-dose glucocorticoids and short-course oral glucocorticoids. Patients were followed up for 3 months. A total of 11 patients were included in the study (average age 56 years). There was no gender difference, but age and underlying diseases could be risk factors for severe influenza virus-associated pneumonia. The types of viruses causing pneumonia included influenza A/B. The main clinical symptoms of patients were fever, cough, sputum production, and dyspnea. Chest computed tomography showed multiple ground-glass shadows in the lobes, and the presence of bacterial and fungal infections was accompanied by consolidation shadows. After glucocorticoid therapy, the symptoms improved. None of the patients underwent tracheal intubation, and all survived. After a 3-month follow-up, lung CT absorption in all patients had reached more than 80%, and lung imaging absorption in 20% patients was complete. No serious complications occurred in any of the patients. Sequential treatment with high-dose steroids and short-course oral glucocorticoids may be helpful for reducing the tracheal intubation rate and mortality rate in patients with severe influenza virus-associated pneumonia. Additionally, short-course oral glucocorticoids may reduce pulmonary fibrosis in patients with severe influenza virus-associated pneumonia without any serious complications.

Therapeutic effects and mechanisms of Modified Ma-Xing-Shi-Gan Decoction on Klebsiella pneumoniae-induced pneumonia in mice assessed by Multi-omics

Ethnopharmacological relevanceModified Ma-Xing-Shi-Gan decoction (MMXSGD), a classic prescription from Treatise on Febrile Disease in China, is commonly used to treat Klebsiella pneumoniae (KP) infections in clinical settings. Materials and methodsThe aim of this study is to assess the efficacy of MMXSGD in the treatment of pneumonia and investigate its underlying mechanism of action. UHPLC-MS/MS was established to identify the main chemical components of serum after intragastric administration with MMXSGD. A mouse model of pneumonia caused by KP was used to evaluate the therapeutic potential of MMXSGD. The macrophage polarization was analyzed by immunohistochemistry. The cytokine profile was assessed using Luminex assay. Lung transcript and metabolite levels were assessed by transcriptomics and non-targeted metabolomics to analyze potential anti-pneumonia mechanisms and targets. Results22 major blood-entry components and 274 MMXSGD-pneumonia-related targets were identified. Compared with the model group, the mortality rate of mice in different dosage groups of MMXSGD was significantly reduced, and pathological lung damage was significantly alleviated. Among them, the low dose of MMXSGD treatment had the best protective effect. Further, MMXSGD treatment could regulates M1/M2 polarization in macrophages and inhibits the production of pro-inflammatory cytokines. The data from transcriptome and metabolome analysis indicate that MMXSGD could regulate inflammation-related pathways (PI3K/AKT, HIF-1, NF-κB pathway) and metabolites to modulate pulmonary inflammation. The results demonstrate that MMXSGD enhances the antibacterial effect in vivo by suppressing inflammation and regulating immunity rather than directly antibacterial effect. ConclusionThese findings provide a further assessment of MMXSGD, suggesting that MMXSGD has good therapeutic efficacy in bacterial infectious diseases.

Predicting Clinical Outcomes in COVID-19 and Pneumonia Patients: A Machine Learning Approach.

In the clinical diagnosis of pneumonia, particularly during the COVID-19 pandemic, individuals who progress to a critical stage requiring mechanical ventilation are classified as mechanically ventilated critically ill patients. Accurately predicting the discharge outcomes for this specific cohort, especially those with COVID-19, is of paramount clinical importance. Missing data, a common issue in medical research, can significantly impact the validity of analyses. In this work, we address this challenge by employing two missing data imputation techniques: multiple imputation and missForest, to enhance data completeness. Additionally, we utilize the smoothly clipped absolute deviation (SCAD) penalized logistic regression method to select significant features. Our real data analysis compares the predictive performances of extreme learning machines, random forests, support vector machines, and XGBoost using 10-fold cross-validation. The results consistently show that XGBoost outperforms the other methods in predicting discharge outcomes, making it a reliable tool for clinical decision-making in the treatment of severe pneumonia, including COVID-19 cases. Within this context, the random forest imputation method generally enhances performance, underscoring its effectiveness in managing missing data compared to multiple imputation.

Chinese expert consensus on diagnosis, treatment and prevention of pulmonary infection in patients with solid tumors (2024 edition)

Patients with solid tumors have an increased risk of developing pneumonia during the management of tumor. The prevention, diagnosis, and treatment of pneumonia in these patients have different characteristics compared to the general population, such as the correction of specific risk factors for pneumonia and the rational use of prophylactic antimicrobial drugs, the strategy of invasive sampling diagnostic techniques application, differential diagnosis from anti-tumor treatment associated pulmonary conditions, and consideration of pathogens and drug resistance in empirical antimicrobial treatment. In order to standardize the diagnosis, treatment, and prevention of pneumonia in patients with solid tumors, Oncology Respiratory Disease Committee initiated the "Chinese expert consensus on the diagnosis and treatment of pneumonia in patients with solid tumors". Based on a review of the latest evidence in this field, the consensus provides diagnostic and treatment pathways as well as recommendations. This consensus applies to oncologists, pulmonologists, infectious disease physicians, surgeons, emergency medicine physician, and general practice healthcare professionals involved in the management of solid tumors in adults.